Impaired IFN-α-mediated signal in dendritic cells differentiates active from latent tuberculosis

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Abstract

Individuals exposed to Mycobacterium tuberculosis (Mtb) may be infected and remain for the entire life in this condition defined as latent tuberculosis infection (LTBI) or develop active tuberculosis (TB). Among the multiple factors governing the outcome of the infection, dendritic cells (DCs) play a major role in dictating antibacterial immunity. However, current knowledge on the role of the diverse components of human DCs in shaping specific T-cell response during Mtb infection is limited. In this study, we performed a comparative evaluation of peripheral blood circulating DC subsets as well as of monocyte-derived Interferon-α DCs (IFN-DCs) from patients with active TB, subjects with LTBI and healthy donors (HD). The proportion of circulating myeloid BDCA3+ DCs (mDC2) and plasmacytoid CD123+ DCs (pDCs) declined significantly in active TB patients compared to HD, whereas the same subsets displayed a remarkable activation in LTBI subjects. Simultaneously, the differentiation of IFN-DCs from active TB patients resulted profoundly impaired compared to those from LTBI and HD individuals. Importantly, the altered developmental trait of IFN-DCs from active TB patients was associated with down-modulation of IFN-linked genes, marked changes in molecular signaling conveying antigen (Ag) presentation and full inability to induce Ag-specific T cell response. Thus, these data reveal an important role of IFN-α in determining the induction of Mtb-specific immunity.

Original languageEnglish
Article numbere0189477
JournalPLoS One
Volume13
Issue number1
DOIs
Publication statusPublished - Jan 1 2018

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Latent Tuberculosis
dendritic cells
tuberculosis
Dendritic Cells
Tuberculosis
Mycobacterium tuberculosis
Interferons
T-cells
Tissue Donors
interferons
infection
Immunity
T-Lymphocytes
Antigens
Mycobacterium Infections
Antigen Presentation
Conveying
T-lymphocytes
immunity
Monocytes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

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title = "Impaired IFN-α-mediated signal in dendritic cells differentiates active from latent tuberculosis",
abstract = "Individuals exposed to Mycobacterium tuberculosis (Mtb) may be infected and remain for the entire life in this condition defined as latent tuberculosis infection (LTBI) or develop active tuberculosis (TB). Among the multiple factors governing the outcome of the infection, dendritic cells (DCs) play a major role in dictating antibacterial immunity. However, current knowledge on the role of the diverse components of human DCs in shaping specific T-cell response during Mtb infection is limited. In this study, we performed a comparative evaluation of peripheral blood circulating DC subsets as well as of monocyte-derived Interferon-α DCs (IFN-DCs) from patients with active TB, subjects with LTBI and healthy donors (HD). The proportion of circulating myeloid BDCA3+ DCs (mDC2) and plasmacytoid CD123+ DCs (pDCs) declined significantly in active TB patients compared to HD, whereas the same subsets displayed a remarkable activation in LTBI subjects. Simultaneously, the differentiation of IFN-DCs from active TB patients resulted profoundly impaired compared to those from LTBI and HD individuals. Importantly, the altered developmental trait of IFN-DCs from active TB patients was associated with down-modulation of IFN-linked genes, marked changes in molecular signaling conveying antigen (Ag) presentation and full inability to induce Ag-specific T cell response. Thus, these data reveal an important role of IFN-α in determining the induction of Mtb-specific immunity.",
author = "Stefania Parlato and Teresa Chiacchio and Debora Salerno and Linda Petrone and Luciano Castiello and Giulia Romagnoli and Irene Canini and Delia Goletti and Lucia Gabriele",
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T1 - Impaired IFN-α-mediated signal in dendritic cells differentiates active from latent tuberculosis

AU - Parlato, Stefania

AU - Chiacchio, Teresa

AU - Salerno, Debora

AU - Petrone, Linda

AU - Castiello, Luciano

AU - Romagnoli, Giulia

AU - Canini, Irene

AU - Goletti, Delia

AU - Gabriele, Lucia

PY - 2018/1/1

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